The cells of the renal nephron and other epithelial tissue selectively transport ions by energy dependent mechanisms. Despite some similarities and the presence of active sodium transport, these tissues manifest widely different electrophysiological characteristics. In particular the high resistance frog skin rectifies current flow, whereas the low resistance renal epithelia do not. Such differences may be accounted for by low resistance shunts between the cells of the renal epithelia. Accordingly these shunts may participate in determining the transepithelial flows of ions. The primary objectives of the proposed studies are to examine the similarities and differences in the electrophysiological behavior of the frog skin with techniques that avoid edge damage and to compare its behavior with that of the isolated perfused rabbit cortical collecting tubule. One of the ideas to be tested will be the idea that transepithelial studies of the skin yield information primarily of the transport processes of the cells, whereas similar studies of the renal tubules yield information of the nature of the shunts between the cells. Together it may be possible to combine the ideas generated from these studies to understand better the physiological relationship between cells and shunts. It may be that under normal physiological conditions drugs and hormones alter the transport characteristics of the tissue by virtue of changes in ionic permeability of the shunts. Thus information so obtained could provide a broader base for understanding the pathophysiology of renal tubular disease.